Systemic Molecular Mediators of Inflammation Differentiate Between Crohn’s Disease and Ulcerative Colitis, Implicating Threshold Levels of IL-10 and Relative Ratios of Pro-inflammatory Cytokines in Therapy

Abstract

Background and AimsFaecal diversion is associated with improvements in Crohn’s disease but not ulcerative colitis, indicating that differing mechanisms mediate the diseases. This study aimed to investigate levels of systemic mediators of inflammation, including fibrocytes and cytokines, [1] in patients with Crohn’s disease and ulcerative colitis preoperatively compared with healthy controls and [2] in patients with Crohn’s disease and ulcerative colitis prior to and following faecal diversion.MethodsBlood samples were obtained from healthy individuals and patients with Crohn’s disease or ulcerative colitis. Levels of circulating fibrocytes were quantified using flow cytometric analysis and their potential relationship to risk factors of inflammatory bowel disease were determined. Levels of circulating cytokines involved in inflammation and fibrocyte recruitment and differentiation were investigated.ResultsCirculating fibrocytes were elevated in Crohn’s disease and ulcerative colitis patients when compared with healthy controls. Smoking, or a history of smoking, was associated with increases in circulating fibrocytes in Crohn’s disease, but not ulcerative colitis. Cytokines involved in fibrocyte recruitment were increased in Crohn’s disease patients, whereas patients with ulcerative colitis displayed increased levels of pro-inflammatory cytokines. Faecal diversion in Crohn’s disease patients resulted in decreased circulating fibrocytes, pro-inflammatory cytokines, and TGF-β1, and increased IL-10, whereas the inverse was observed in ulcerative colitis patients.ConclusionsThe clinical effect of faecal diversion in Crohn’s disease and ulcerative colitis may be explained by differing circulating fibrocyte and cytokine responses. Such differences aid in understanding the disease mechanisms and suggest a new therapeutic strategy for inflammatory bowel disease.

Adults with Crohn’s disease exhibit elevated gynoid fat and reduced android fat irrespective of disease relapse or remission

“…More specifically, in light of preferential deposition of adipose tissue in hips and upper thighs of patients with CD, it is reasonable to argue that fat wrapping of inflamed intestinal tissue in the abdominal area deserves even greater attention than is currently focused. While mesenteric fat has been recognised as a potential barrier to inflammatory markers, to mitigate bacterial transposition and a reservoir of inflammatory adipokines 29 , 36 , we suggest tentatively that this juxtaposition of organ-specific and regional adiposity represents a rationale to refer to Crohn’s disease as a non-alcoholic fatty intestine condition, albeit that our data represent early insights limited to pilot-scale.…”

Chitin Glucan Shifts Luminal and Mucosal Microbial Communities, Improve Epithelial Barrier and Modulates Cytokine Production In Vitro

“…The impaired epithelial barrier has been associated with inflammatory pathological conditions of the gut and restoration of intestinal function has been proposed as a potential therapeutic target to promote recovery of intestinal homeostasis [ 51 ]. Recently, a microbial anti-inflammatory molecule (MAM) produced by F. prausnitzii efficiently re-established the intestinal barrier structure via the regulation of the tight junction pathway and ZO-1 expression [ 52 ], while previous studies also showed that F. prausnitzii is associated with anti-inflammatory effects via IL10 induction in dendritic cells [ 53 ]. Roseburia intestinalis and bifidobacteria have also been described as effective commensals in promoting intestinal barrier function [ 54 , 55 , 56 ].…”

Mycobacterial Hsp65 antigen delivered by invasive Lactococcus lactis reduces intestinal inflammation and fibrosis in TNBS-induced chronic colitis model

“…This result possibly explains the inflammation scores and decreased histological features of the NFXi group. Notably, IL-10 is an influential interleukin that can modulate pro-and anti-inflammatory cytokines 38 , and IL-10 can also suppress exacerbated mucosal immune responses, maintain intestinal homeostasis and tolerance to commensal microbiota 39 and inhibit collagen deposition in the host intestine 30 .…”